rs288293

Positions:

• chr2-182766793-G-A
• chr2-182766793-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018981.4(DNAJC10):​c.2265+3992G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 151,888 control chromosomes in the GnomAD database, including 31,876 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (31876 hom., cov: 30)
• Consequence: DNAJC10 NM_018981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

Genes affected

DNAJC10 (HGNC:24637): (DnaJ heat shock protein family (Hsp40) member C10) This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAJC10	NM_018981.4	c.2265+3992G>A		intron_variant		ENST00000264065.12	NP_061854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAJC10	ENST00000264065.12	c.2265+3992G>A		intron_variant		1	NM_018981.4	ENSP00000264065	P1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97824 AN: 151770 Hom.: 31853 Cov.: 30

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.676

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 97883 AN: 151888 Hom.: 31876 Cov.: 30 AF XY: 0.641 AC XY: 47632 AN XY: 74264

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.780

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.673

Alfa AF: 0.605 Hom.: 9284

Bravo AF: 0.638

Asia WGS AF: 0.587 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs288293; hg19: chr2-183631520;